Elimination reactions 2,3-dihydrofuran

However, considerable amounts of 2,3-dihydrofuran 50 and tetrahydro-furan-2-carbaldehyde 53 were present because of an isomerization process. The isomerization takes place simultaneously with the hydroformylation reaction. When the 2,5-dihydrofuran 46 reacts with the rhodium hydride complex, the 3-alkyl intermediate 48 is formed. This can evolve to the 2,3-dihydrofuran 50 via /3-hydride elimination reaction. This new substrate can also give both 2- and 3-alkyl intermediates 52 and 48, respectively. Although the formation of the 3-alkyl intermediate 48 is thermodynamically favored, the acylation occurs faster in the 2-alkyl intermediates 52. Regio-selectivity is therefore dominated by the rate of formation of the acyl complexes. The modification of the phosphorus ligand and the conditions of the reaction make it possible to control the regioselectivity and prepare the 2- or 3-substituted aldehyde as the major product [78]. As far as we know, only two... 

Scheme 6 shows the two possible modes for coordination of 2,3-dihydrofuran to the [PdPh (R)-BINAP ]+ species. As suggested from the molecular model in Figure 1, dihydrofuran may coordinate to the palladium center more easily in mode (a) than (b). The olefin-coordination in mode (a) followed by olefin-insertion and p-hydrogen elimination reactions forms the phenylation product having (/ -configuration, that is the observed configuration in major regioisomer 2 in the actual catalytic reactions. 

A simple procedure to prepare 5-aryl- and 5-pyridyl-2-furaldehydes from inexpensive, commercially available 2-furaldehyde diethyl acetal was reported. The reaction proceeded in a four-step, one-pot procedure and the yield of coupling step was usually between 58-91% <02OL375>. A facile route to 3,4-furandicarboxylic acids was developed. DDQ-oxidation of 2,5-dihydrofuran derivatives, which were produced from dimethyl maleic anhydride, furnished the desired esters of furan-3,4-dicarboxylic acid <02S1010>. The furan-fused tetracyclic core of halenaquinol and halenaquinone possessing antibiotic, cardiotonic, and protein tyrosine kinase inhibitory activities was synthesized. Intramolecular cycloaddition of an o-quinodimethane with furan gave the adduct as a single isomer via an enrfo-transition state, which was converted to trisubstituted furan by oxidation-elimination reactions <02T6097>. 

Elimination of hydrogen bromide from 1,2-dibromo-4-butanol, BrCHjCHBrCHjCHjOH, is accomplished with powdered potassium hydroxide in dry ether. The resulting /3-bromotetrahydrofuran loses another molecule of hydrogen halide when heated with excess powdered base. The over-all yield of dihydrofuran is 62%. This elimination reaction has been extended to the preparation of /3-bromofurans and 2,5-dihydrofurans having two alkyl groups on one of the a-carbon atoms. ... 

When these reaction conditions were employed to oxidative addition of aldehydes with 1,3-indandione 149, different type of product was obtained, the bispiro-snbstituted cyclopropanes 150 exclusively and in good yields (Scheme 2.52, Table 2.46). Model reactions carried out in dioxane solvent gave the same prodncts, but after 1 h the yields were lower. The reaction mechanism is thought to start with Knoevenagel condensation, followed by iodination, and intramolecnlar nucleophilic 0-attack with HI elimination to dihydrofurans. When intramolecnlar nucleophilic C-attack occurs, with subsequent elimination of HI, cyclopropanes were prodnced. 

FIGURE 6.5 Analysis of elimination reactions in dihydrofurans by PMO approach. 

The final variation of the Feist-Benary furan synthesis encompasses reactions of 1,3-dicarbonyls with 1,2-dibromoethyl acetate (52). For example, treatment of ethyl acetoacetate (9) with sodium hydride followed by addition of 52 at 50°C yields dihydrofuran 53. The product can be easily converted into the corresponding 2-methyl-3-furoate upon acid catalyzed elimination of the acetate, thus providing another strategy for the synthesis of 2,3-disubstituted furans. 

In 1996, the first examples of intermolecular microwave-assisted Heck reactions were published [85]. Among these, the successful coupling of iodoben-zene with 2,3-dihydrofuran in only 6 min was reported (Scheme 75). Interestingly, thermal heating procedures (125-150 °C) resulted in the formation of complex product mixtures affording less than 20% of the expected 2-phenyl-2,3-dihydrofuran. The authors hypothesize that this difference is the result of well-known advantages of microwave irradiation, e.g., elimination of wall effects and low thermal gradients in the reaction mixture. 

Furans. Reaction of a,a-dimethoxy ketones with 1 affords a dihydrofuran (2) presumably via a carbene (a) that inserts intramolecularly into a C—H of an adjacent methoxy group. The reaction often results directly in a furan, since the elimination of methanol from 2 is facile. 

Palladium-catalyzed reaction of a 3,4-allenol with iodobenzene proceeds through an oxypalladation-reductive elimination sequence to give a 2,3-dihydrofuran efficiently (Scheme 16.8) [13,14],... 

Bis(5> m-collidine)iodine(I) tetrafluoroborate in DMSO has been found to be a convenient reagent for the conversion of alkanes to a-iodocarbonyl compounds. When dihydrofuran (305a) and dihydropyran (305b) are the substrates, this reaction affords the corresponding a-iodolactones 306 (Scheme 77). This method converts certain glycals such as 307 to their corresponding a-iodo-a,/3-unsaturated lactones 309, presumably because of elimination of a molecule of acetic acid from the initially formed lactone 308 (86S727) (Scheme 78). 

An efficient way to attach carboxylic acid derivatives directly to Cgg was found with the reaction of the corresponding diazoketones 158-162 with Cgg in toluene or methybiaphthalene at elevated temperatures [133]. The [6,6] closed cycloaddition products are formed in moderate yields although a significant amount of a side-product was produced. This side-product was found to be a dihydrofuran fused CgQ-adduct The direct reaction product of the malic acid derivative 162 without elimination of AcO H could not be isolated instead the trans-alkene 163 was formed and isolated in 18% yield. 

Dimethylene-2,3-dihydrofuran derivatives, which are produced by fluoride-induced 1,4-conjugative elimination of trimethylsilyl acetate from the [(trimethylsilyl)methyl]-3-furan precursor 207, undergo subsequent [4-1-4] dimerization reactions to produce cycloocta[l,2-3 6,5-. ]difuran derivatives as a mixture of isomers (Equation 137) <1995JA841 >. A methyl substituent at the 3-methylene position was found to retard the rate of dimerization, an observation which is consistent with the proposed two-step mechanism involving the initial formation of a diradical intermediate in the rate-determining step (Table 16). 

The absence of a hydroxyl group from C-2 makes elimination of the 4-hydroxyl group impossible, but two other reactions are possible for 57. The more important is, apparently, the formation, between C-l and C-4, of a 2,5-dihydrofuran ring that is readily dehydrated to the furan. A competitive reaction, namely, the elimination of the 5-hydroxyl group by an extended enolization, would lead to formation of carbocyclic compounds. 

The formation both of 5-formyl-2-furoic acid (74) and 2-furaldehyde could result by way of the formation of the 2,5-dihydrofuran 73. Elimination of the C-5 proton and the 2-hydroxyl group by a reaction analogous to that for the formation of 5-(hydroxymethyl)-2-furalde-hyde yields 74, whereas decarboxylation, as shown, results in 2-furaldehyde. Once formed, 73 would be expected to give higher yields of 74 than of 27 this implies that decarboxylation occurs prior to ring formation. 

The methylation of sulfoximines 45 with Me30BF4 proceeded readily and gave the corresponding cyclic aminosulfoxonium salts 46 in quantitative yields. Upon treatment with LiN(H)t-Bu first at-78 °C and then at room temperature, salts 46 delivered the enantio- and diastereomerically pure bicyclic 2,3-dihydrofurans 50 cleanly in high overall yields. It is proposed that the reactions of the aminosulfoxonium salts 40 and 46 with the lithium amide at low temperatures afford the vinyl aminosulfoxonium ylides 41 and 47, respectively. These alkylidene carbenoids eliminate sulfinamide 35 at higher temperatures with formation of the alkylidene carbenes 42 and 48, respectively. Subsequently, the alkylidene... 

As mentioned previously, the partially reduced forms of five membered heteroaromatic systems might act as olefins in insertion reactions. This behaviour is characteristic particularly of dihydrofuranes. The olefin insertion and the following / hydride elimination should in principle lead to a trisubstituted olefin, which is rarely observed, however. Typical products of this reaction are 2-aryl-2,3-dihydrofuranes. A characteristic example of such a reaction is presented in 6.54. The coupling of 4-iodoanisole and dihydrofurane led to the formation of the chiral 2-anisyl-2,3-dihydrofurane in excellent yield.83 The shift of the double bond, which leads to the creation of a new centre of chirality in the molecule, opens up the way for enantioselective transformations. Both intermolecular and intramolecular variants of the asymmetric Heck reaction have been studied extensively.84... 

Acyloins undergo nucleophilic addition to /3-ethoxyvinylphosphonium salts (141) to yield an ylide (142) (74JOC584). Intramolecular Wittig reaction results in formation of the dihydrofuran (143), which is converted to the furan (144) by elimination of ethanol (Scheme 32). Symmetric acyloins give one product, but unsymmetrical ones may give two products under basic conditions due to tautomerization. 

Asymmetric Fleck reactions have been carried out with considerable success. The arylation of 2,3-dihydrofuran (38) with phenyl triflate using BINAP (XXXI) as a chiral ligand gave 2-phenyl-2,3-dihydrofuran (42) with 96% ee. Addition of FI—Pd—X to the primary product 40 gives the intermediate 41, and /f-elimination affords the dihydrofuran 42 with 96% ee in 71% yield as the major product in the presence of l,8-bis(dimethylamino)naphthalene (39) as a base. Another dihydrofuran 40 with 67% ee was obtained in 7%, showing that one enantiomer of 40 is converted to 42 with high selectivity [24]. 

As p-hydride elimination is reversible, hydropalladation with the opposite regiochemistry provides a mechanism for forming regioisomers of the alkene. This allows the most stable alkene that is accessible by the hydropalladation-dehydropalladation sequence to dominate. The only restriction is that all of these processes are syn. The migration can be prevented by the addition of bases like silver carbonate, which effectively removes the hydrogen halide from the palladium complex as soon as it is formed. This synthesis of a complex trans dihydrofuran involves the Heck reaction followed by alkene isomerization and then a Heck reaction without migration to preserve the stereochemistry. 

Via Elimination of A kohol or W alter from Dihydrofurans Pyrolysis of 2,5-dialkoxy- or -diacetoxy-2,5-dihydrofurans results in a smooth reaction with the formation of 2-substituted furans.39 40... 

Coupling of 2,3-dihydrofuran with alkene-zirconocene <2004AGE3932> or aryne-zirconocene <2005SL2513> complexes and subsequent addition of an electrophile provided rA-disubstituted homoallylic alcohols, as illustrated in Equation (130). An insertion//3-elimination pathway that involved the formation of an oxazirconacyclooctene intermediate was proposed for the reaction mechanism. 

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